The present invention relates to liquid viral vaccines. More particularly it relates to a stabilizer for liquid viral vaccines.
Due to the worldwide distribution of vaccines and the diversity of ambient temperatures, there has been a need to stabilize these preparations for transportation and use. Several stabilization methods have been used in the past.
(a) Low temperatures (-10.degree. C. to -70.degree. C.).
The need for low temperature storage facilities which are not always available limits the practicality of this approach.
(b) Lyophilization
Although lyophilization suffers the disadvantages of being an expensive procedure, lyophilized vaccines are reasonably stable and are stored at 4.degree.-8.degree. C. until needed. During this storage period, however, the vaccine slowly deteriorates until after about 12-24 months it does not have sufficient titer to confer immunization. Furthermore, since the lyophilized vaccine must be reconstituted prior to use, the liquid reconstituted preparation loses potency while standing at room temperature. This can result in insufficient titer to confer immunity and results in failure of immunization program.
(c) Stabilizers
These are chemical compounds added to the vaccine and are used in conjunction with either lower temperature storage or lyophilization methods. Chemical stabilizers, e.g., SPGA (a stabilizer described by Bovarnick et al., J. Bact. 59:509-522 (1950), the disclosure of which is incorporated herein by reference) and the like are described in the prior art. As described by Bovarnick et al. a liter of SPGA contains 0.218 M sucrose (74.62 g), 0.00376 M KH.sub.2 PO.sub.4 (0.52 g), K.sub.2 HPO.sub.4 0.0071 M (1.25 g), potassium glutamate 0.0049 M (0.912 g) and 1% serum albumin (10 g). Various modifications of the foregoing amounts of ingredients of SPGA are known to those skilled in the art and sodium glutamate is frequently substituted for potassium glutamate, but the modified compositions are still designated as SPGA. For example, U.S. Pat. No. 3,783,098 refers to an SPGA stabilizer containing monosodium glutamate rather than monopotassium glutamate (col. 6, lines 5-11). U.S. Pat. No. 4,002,256 describes an SPGA stabilizer containing per liter of sterile distilled water, 74.62 g sucrose, 0.45 g KH.sub.2 PO.sub.4, 1.35 g K.sub.2 HPO.sub.4, 0.956 g monosodium L-glutamate, and 40 ml of a 25% solution of albuminosol (human albumin). In general an SPGA stabilizer contains from about 2 to about 10% of sugar, e.g. sucrose; from about 0.05 to about 0.3% of a mono- or dibasic alkali metal phosphate salt or mixture thereof, e.g. KH.sub.2 PO.sub.4, K.sub.2 HPO.sub.4, NaH.sub.2 PO.sub.4, or Na.sub.2 HPO.sub.4, from about 0.05 to about 0.2% of a glutamic acid alkali metal salt, e.g. sodium or potassium glutamate; and from about 0.5% to about 2% serum albumin, e.g. bovine serum albumin or human albumin. Various substitutions of ingredients in the formulation of SPGA stabilizer can be made. For example, a starch hydrolysate, e.g. glucose or dextran may be substituted wholly or partly for sucrose as disclosed in U.S. Pat. No. 3,783,098, (col. 3, lines 59-61) and casein or PVP may be substituted wholly or partly for albumin as described, respectively, in U.S. Pat. No. 3,783,098 (col. 3, line 8) and U.S. Pat. No. 3,915,794. None of the prior art stabilizers, however, imparts the desired enhanced sustained level of stability.